Herpes zoster (HZ) or shingles is a serious health problem occurring in one of three adults during their life time, nearly one million cases a year in the United States. Almost 23-50% of individuals, who acquire herpes zoster (HZ), develop complications including debilitating zoster-associated pain and/or serious non-pain complications. The currently available zoster vaccine is recommended only for immunocompetent adults 60 years or older and it is not recommended for selected risk groups among adults younger than 60 years of age. Our recently completed pilot study showed that children with asthma or other atopic conditions had significantly increased risks of HZ compared to those without such conditions. The mechanisms involved in this association are unknown. However, because cell-mediated immunity plays a key role for preventing HZ and we found that children with asthma had poorer cell-mediated immune responses to measles, mumps, and rubella vaccine viruses, this association might be biologically plausible. This is further supporte by our study findings (R01A156133) that adults with asthma or other atopic conditions are at significantly increased risk of a bacterial infection- serious pneumococcal disease. At present, it is unknown whether this association between asthma and HZ observed in children is true for adults. The main goal of this study is to determine risk and complications of HZ in individuals with or without asthma. This goal will be accomplished by comparing the frequency of asthma among HZ cases and their age- and gender-matched controls (Aim 1). Complications of HZ will be determined by comparing the frequency of HZ-associated complications between individuals with and those without asthma among HZ cases (Aim 2). We hypothesize that adults with asthma have a higher risk of HZ as compared to those without asthma. Also, we believe that adults with asthma are more likely to develop complications of HZ than those without asthma. The implications of our study include: First, given the significant morbidity related to HZ among affected adults, efficacy, and safety of HZ vaccine, and a significant proportion of people affected by asthma in a population, our study results may help us determine whether people age younger than 60 years with asthma should be considered a selective risk group for HZ and immunized with zoster vaccine. This knowledge may ultimately help to lower the targeted age group for zoster vaccine so that people age younger than 60 years with high-risk conditions for HZ can be eligible for zoster vaccine. Second, our study results are important for understanding a systemic immune effect of asthma on cell-mediated immunity against pathogens. Third, the results of this epidemiologic study is likely to guide the mechanistic studies to unravel how the immunologic underpinnings of atopic conditions is related to the mechanisms associated with the increased risk of HZ in people with asthma or other atopic conditions. This may lead to novel prevention or management strategies. PUBLIC HEALTH RELEVANCE: One of three adults in the United States develop shingles during their life time. It can cause serious infections and complications in 23 to 50% of those infected. The currently available vaccine reduces risk of shingles and post-herpetic neuralgia. It is approved for immunocompetent adult 50 years or older but only recommended for those 60 years or older by the Advisory Committee on Immunization Practices. Our recent study showed that children with asthma, eczema, or nasal allergy have a significantly increased risk of shingles, as compared to those without these allergic conditions. Whether this association is true for adults is unknown. In our study application, we will examine whether adults with asthma have an increased risk of shingles and its complications, compared to those without asthma. We believe this information is crucial for determining whether younger individuals with asthma, who are not eligible for the current vaccine for shingles, should receive the vaccine for shingles in te future. This information is also important for advancing our understanding of the disease nature of asthma as a systemic disease beyond a chronic airway disease and the underpinnings of asthma and other allergic diseases.